Antibiotic resistance is recognized as one of the greatest threats to human health on the planet (2009; Choffnes et al., Antibiotic Resistance: Implications for Global Health and Novel Intervention Strategies, The National Academic Press, Washington, D.C., (2010); Smolinski et al., Microbial Threats to Health: Emergence, Detection, and Response, The Institute of Medicine, Washington D.C., (2003); Spellberg et al., Clin Infect Dis 52(55):397-428 (2011); Spellberg et al., Clin Infect Dis 46:155-164 (2008); Walker et al., Science 325-1345-1346 (2009). In the last decade, Acinetobacter baumannii has emerged as one of the most common and highly antibiotic-resistant pathogens in the United States (US) and throughout the world (Doi et al., Emerg Infect Dis 15:980-982 (2009); Higgins et al., J Antimicrob Chemother 65-233-238 (2010); Perez et al., Antimicrob Agents Chemother 51:3471-3484 (2007). Indeed, 50-70% of A. baumannii clinical isolates are now extensively drug resistant (XDR; i.e. resistant to carbapenems and all other antibiotics except colistin or tigecycline), reflecting a >15-fold increase in just the past 10 years (Dizbay et al., Scand J Infect Dis (2010); Hidron et al., Infect Control Hosp Epidemiol 29:996-1011 (2008); Hoffmann et al., Infect Control Hosp Epidemiol 31:196-197 (2010); Kallen et al., Infect Control Hosp Epidemiol 31:528-531 (2010); Lautenbach et al., Infect Control Hosp Epidemiol 30:1186-1192 (2009); Mera et al., Drug Resist 16:209-215 (2010); Perez et al., Am J Infect Control 38:63-65 (2010); Rosenthal et al., Am J Infect Control 38:95-104 e102 (2010). Infections caused by carbapenem-resistant, XDR A. baumannii are associated with prolonged hospitalization, tremendous health care costs, and high rates of death despite treatment (Doi et al., Emerg Infect Dis 15:980-982 (2009); Falagas et al., Int J Antimicrob Agents 32:450-454 (2008); Gordon and Wareham, J Antimicrob Chemother 63:775-780 (2009); Lautenbach et al., Infect Control Hosp Epidemiol 30:1186-1192 (2009); Metan et al., Eur J Intern Med 20:540-544 (2009); Park et al., Diagn Microbiol Infect Dis 64:43-51 (2009); Perez et al., Am J Infect Control 38:63-65 (2007); Sunenshine et al., Emerg Infect Dis 13:97-103 (2007). Indeed, bloodstream infections caused by XDR A. baumannii cause >50-60% mortality rates despite antibiotic therapy (Gordon and Wareham, J Antimicrob Chemother 63:775-780 (2009); Metan et al., Eur J Intern Med 20:540-544 (2009); Munoz-Price et al., Infect Control Hosp Epidemiol 1(10):1057-62 (2010); Park et al., Diagn Microbiol Infect Dis 64:43-51 (2009); Tseng et al., Diagn Microbiol Infect Dis 59:181-190 (2007). A major reason for these high mortality rates is that XDR A. baumannii infections are treatable only with suboptimal second-line antibacterial agents, such as tigecycline and colistin. Even more concerning is the increasing resistance of A. baumannii to both colistin and tigecycline (Adams et al., Antimicrob Agents Chemother 53:3628-3634 (2009); Doi et al., Emerg Infect Dis 15:980-982 (2009); Falagas et al., Int J Antimicrob Agents 32:450-454 (2008); Hernan et al., Diagn Microbiol Infect Dis 65:188-191 (2009); Livermore et al., Int J Antimicrob Agents 35:19-24 (2010); Park et al., Diagn Microbiol Infect Dis 64:43-51 (2009); Valencia et al., Infect Control Hosp Epidemiol 30:257-263 (2009); Wang and Dowzicky, Diagn Microbiol Infect Dis 68:73-79 (2010). Such pan-drug resistant (PDR) A. baumannii infections are resistant to every FDA approved antibiotic, and are hence untreatable.
New methods to prevent such XDR/PDR A. baumannii infections are critically needed, especially since no new drugs to treat these infections are in the antibacterial pipeline for the coming decade (Boucher et al., Clin Infect Dis 48:1-12 (2009); Spellberg et al., Clin Infect Dis 46:155-164 (2008). Since risk factors for A. baumannii infections are understood (Beavers et al., 2009; Caricato et al., Intensive Care Med 35:1964-1969 (2009); D'Agata et al., Infect Control Hosp Epidemiol 21:588-591 (2000); Furniss et al., J Burn Care Rehabil 26:405-408 (2005); Metan et al., Eur J Intern Med 20:540-544 (2009); Zakuan et al., Trop Biomed 26:123-129 (2009), vaccination of acutely at-risk patients is a promising method to prevent such infections, and antibody-based immunotherapy has promise to improve outcomes from infection.